tbuckley/cabot-search huggingface dataset:
Turning on the light for brain tumor surgery: A 5-aminolevulinic acid story
Authors: David J McCracken, Alexander J Schupper, Nikita Lakomkin, James Malcolm, David Painton Bray, Constantinos G Hadjipanayis
Journal: Neuro-Oncology (2022)

To aid surgeons in more complete and safe resection of brain tumors, adjuvant technologies have been developed to improve visualization of target tissue. Fluorescence-guided surgery relies on the use of fluorophores and specific light wavelengths to better delineate tumor tissue, inflammation, and areas of blood-brain barrier breakdown. 5-aminolevulinic acid (5-ALA), the first fluorophore developed specifically for brain tumors, accumulates within tumor cells, improving visualization of tumors both at the core, and infiltrative margin. Here, we describe the background of how 5-ALA integrated into the modern neurosurgery practice, clinical evidence for the current use of 5-ALA, and future directions for its role in neurosurgical oncology. Maximal safe resection remains the standard of care for most brain tumors. Gross total resection of high-grade gliomas (HGGs) is associated with greater overall survival and progression-free survival (PFS) in comparison to subtotal resection or adjuvant treatment therapies alone.1-3 A major challenge neurosurgeons encounter when resecting infiltrative gliomas is identification of the glioma tumor margin to perform a radical resection while avoiding and preserving eloquent regions of the brain. 5-aminolevulinic acid (5-ALA) remains the only optical-imaging agent approved by the FDA for use in glioma surgery and identification of tumor tissue.4 A multicenter randomized, controlled trial revealed that 5-ALA fluorescence-guided surgery (FGS) almost doubled the extent of tumor resection and also improved 6-month PFS.5 In this review, we will highlight the current evidence for use of 5-ALA FGS in brain tumor surgery, as well as discuss the future directions for its use.
Safety and patterns of survivorship in recurrent GBM following resection and surgically targeted radiation therapy: Results from a prospective trial
Authors: Kris Smith, Peter Nakaji, Theresa Thomas, Dilini Pinnaduwage, Garrick Wallstrom, Mehee Choi, Joseph Zabramski, Clark Chen, David Brachman
Journal: Neuro-Oncology (2022)

Treatment of recurrent glioblastoma (GBM) remains problematic with survival after additional therapy typically less than 12 months. We prospectively evaluated whether outcomes might be improved with resection plus permanent implantation of a novel radiation device utilizing the gamma-emitting isotope Cs-131 embedded within bioresorbable collagen tiles.
Early Childhood Education: Health, Equity, and Economics
Authors: Robert A. Hahn, W. Steven Barnett
Journal: Annual Review of Public Health (2022)

Many low-income and minority children in the United States and globally are at risk of poor educational trajectories and, consequently, diminished life courses, because their households and neighborhoods lack resources to adequately support learning and development prior to formal schooling. This review summarizes evidence on center-based early childhood education (ECE) for three- and four-year-olds as a means of assuring school readiness in cognitive and socioemotional skills. While the details of ECE programs merit further research, it is clear that ECE can benefit children, especially those most disadvantaged, with additional societal benefits and positive long-run economic returns. Universal ECE is not a cure-all, and its success requires ongoing alignment with subsequent education and attention to child household and community conditions. Because resource deprivation is concentrated in low-income and minority communities, publicly funded universal ECE can also be a powerful instrument for the promotion of social equity.
Laser hyperthermia: Past, present, and future
Authors: Alexander J Schupper, Tori Chanenchuk, Anna Racanelli, Gabrielle Price, Constantinos G Hadjipanayis
Journal: Neuro-Oncology (2022)

Abstract Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is an ablative procedure using heat from a laser to provide cytoreduction in tissue. It is a minimally invasive procedure that has been used in intracranial pathologies such as high-grade gliomas, metastatic lesions, epilepsy, and other lesions. While LITT may offer a more acceptable complication profile compared to open surgery, the role of laser therapy for intracranial lesions in current treatment paradigms continues to evolve. This review will focus on the background and application of LITT, the current evidence for its use, and future directions for the technology.
Treatment of Uncomplicated Type B Aortic Dissection
Authors: Karen M. Kim, Marion A. Hofmann Bowman, Kim A. Eagle
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Population-Level Implications of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Preserved Ejection Fraction in the US
Authors: Khawaja M. Talha, Javed Butler, Stephen J. Greene, Rahul Aggarwal, Stefan D. Anker, Brian L. Claggett, Scott D. Solomon, John J. V. McMurray, Muthiah Vaduganathan, Gregg C. Fonarow
Journal: JAMA Cardiology (2022)

The expansion of sodium-glucose cotransporter-2 (SGLT-2) inhibitor use in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) more than 40% following the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) and the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials have major implications in the US.
The benefit of macrolide therapy in patients with pneumococcal pneumonia is only present in patients with bacteremia
Authors: J. Gonçalves-Pereira, L. Costa, I. Silva, A. Simões, F. Froes, P. Mergulhão, P. Varela Ramos, D. Leal, R. Alves, M. Custódio, A. Gomes
Journal: Pulmonology (2022)
The Dynamics of Adaptation to Stress from Standing Genetic Variation and de novo Mutations
Authors: Sandra Lorena Ament-Velásquez, Ciaran Gilchrist, Alexandre Rêgo, Devin P Bendixsen, Claire Brice, Julie Michelle Grosse-Sommer, Nima Rafati, Rike Stelkens
Journal: Molecular Biology and Evolution (2022)

Abstract Adaptation from standing genetic variation is an important process underlying evolution in natural populations, but we rarely get the opportunity to observe the dynamics of fitness and genomic changes in real time. Here, we used experimental evolution and Pool-Seq to track the phenotypic and genomic changes of genetically diverse asexual populations of the yeast Saccharomyces cerevisiae in four environments with different fitness costs. We found that populations rapidly and in parallel increased in fitness in stressful environments. In contrast, allele frequencies showed a range of trajectories, with some populations fixing all their ancestral variation in &amp;lt;30 generations and others maintaining diversity across hundreds of generations. We detected parallelism at the genomic level (involving genes, pathways, and aneuploidies) within and between environments, with idiosyncratic changes recurring in the environments with higher stress. In particular, we observed a tendency of becoming haploid-like in one environment, whereas the populations of another environment showed low overall parallelism driven by standing genetic variation despite high selective pressure. This work highlights the interplay between standing genetic variation and the influx of de novo mutations in populations adapting to a range of selective pressures with different underlying trait architectures, advancing our understanding of the constraints and drivers of adaptation.
Fabricating 3-dimensional human brown adipose microtissues for transplantation studies
Authors: Ou Wang, Li Han, Haishuang Lin, Mingmei Tian, Shuyang Zhang, Bin Duan, Soonkyu Chung, Chi Zhang, Xiaojun Lian, Yong Wang, Yuguo Lei
Journal: Bioactive Materials (2022)

Transplanting cell cultured brown adipocytes (BAs) represents a promising approach to prevent and treat obesity (OB) and its associated metabolic disorders, including type 2 diabetes mellitus (T2DM). However, transplanted BAs have a very low survival rate in vivo. The enzymatic dissociation during the harvest of fully differentiated BAs also loses significant cells. There is a critical need for novel methods that can avoid cell death during cell preparation, transplantation, and in vivo. Here, we reported that preparing BAs as injectable microtissues could overcome the problem. We found that 3D culture promoted BA differentiation and UCP-1 expression, and the optimal initial cell aggregate size was 100 μm. The microtissues could be produced at large scales via 3D suspension assisted with a PEG hydrogel and could be cryopreserved. Fabricated microtissues could survive in vivo for long term. They alleviated body weight and fat gain and improved glucose tolerance and insulin sensitivity in high-fat diet (HFD)-induced OB and T2DM mice. Transplanted microtissues impacted multiple organs, secreted protein factors, and influenced the secretion of endogenous adipokines. To our best knowledge, this is the first report on fabricating human BA microtissues and showing their safety and efficacy in T2DM mice. The proposal of transplanting fabricated BA microtissues, the microtissue fabrication method, and the demonstration of efficacy in T2DM mice are all new. Our results show that engineered 3D human BA microtissues have considerable advantages in product scalability, storage, purity, safety, dosage, survival, and efficacy.
Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial
Authors: Hope S. Rugo, Seock-Ah Im, Fatima Cardoso, Javier Cortes, Giuseppe Curigliano, Antonino Musolino, Mark D. Pegram, Thomas Bachelot, Gail S. Wright, Cristina Saura, Santiago Escrivá-de-Romaní, Michelino De Laurentiis, Gary N. Schwartz, Timothy J. Pluard, Francesco Ricci, William R. Gwin, Christelle Levy, Ursa Brown-Glaberman, Jean-Marc Ferrero, Maaike de Boer, Sung-Bae Kim, Katarína Petráková, Denise A. Yardley, Orit Freedman, Erik H. Jakobsen, Einav Nili Gal-Yam, Rinat Yerushalmi, Peter A. Fasching, Peter A. Kaufman, Emily J. Ashley, Raul Perez-Olle, Shengyan Hong, Minori Koshiji Rosales, William J. Gradishar
Journal: Journal of Clinical Oncology (2022)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711 ), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2–positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2–positive breast cancer with different CD16A allelic variants are warranted.
Radiation Therapy for Low-Risk Breast Cancer: Whole, Partial, or None?
Authors: Meena S. Moran, Alice Y. Ho
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. The following case represents a relatively common clinical scenario of a postmenopausal female patient who presents with low-risk, estrogen receptor–positive/progesterone receptor–positive/human epidermal growth factor receptor 2–negative, early-stage, left-sided breast cancer to discuss the role of postoperative radiation (RT) following wide local excision (WLE) and sentinel node biopsy. The spectrum of choices, ranging from omission of RT, accelerated partial breast irradiation (PBI), whole-breast radiation therapy, and the nuances of various dose/fractionation regimens for each option, are discussed in the context of the Danish Breast Cancer Study Group (DBCSG) PBI trial published in this issue, with additional review of other key trials that inform these treatment recommendations. After consideration of the clinical-pathologic features in the framework of the existing data and an in-depth discussion taking into consideration the patient's preferences/goals, the decision was made to deliver moderately hypofractionated RT (40 Gy/15 fractions) to a PBI volume, in concordance with the DBCSG-PBI trial.
Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial
Authors: Jacobus Pfisterer, Florence Joly, Gunnar Kristensen, Joern Rau, Sven Mahner, Patricia Pautier, Ahmed El-Balat, Jean-Emmanuel Kurtz, Ulrich Canzler, Jalid Sehouli, Martin L. Heubner, Andreas D. Hartkopf, Klaus Baumann, Annette Hasenburg, Lars C. Hanker, Antje Belau, Barbara Schmalfeldt, Dominik Denschlag, Tjoung-Won Park-Simon, Frédéric Selle, Christian Jackisch, Alexander Burges, Hans-Joachim Lück, Günter Emons, Werner Meier, Martina Gropp-Meier, Willibald Schröder, Nikolaus de Gregorio, Felix Hilpert, Philipp Harter
Journal: Journal of Clinical Oncology (2022)

PURPOSE To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer. METHODS In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890 ), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m 2 plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability. RESULTS Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank P = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; P = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab. CONCLUSION Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.
Onco-Hypertension: Changing Paradigm of Treating Hypertension in Patients With Cancer
Authors: Gagan Sahni
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. Hypertension (HTN) in patients with cancer remains an underestimated yet complex clinical conundrum to merit its own marker of Onco-Hypertension. A myriad of antineoplastic drugs from vascular endothelial growth factor (VEGF) inhibitor antibodies such as bevacizumab, tyrosine kinase inhibitors (TKIs), cisplatin, and carfilzomib cause new or worsening HTN, and HTN is also a risk factor for certain cancers such as renal cell carcinoma. Untreated HTN before and during cancer treatment potentially increases the short-term and long-term risk of cardiotoxicity, such as heart failure, and affects both cancer and cardiovascular mortality. However, efficient and early management of HTN in patients with cancer is often challenging because of multiple drug interactions, noncompliance, and intolerance of medications because of the side effects of cancer treatments, labile nature of HTN, use of non-neoplastic drugs such as steroids and erythropoietin, and pharmacogenetic interactions between cancer treatment and HTN-related genes. The Oncology Grand Rounds aim to examine the bidirectional association and challenges of managing HTN in patients with cancer and the necessity for precision medicine to manage it.
A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination
Authors: Mark Canney, Mohammad Atiquzzaman, Amanda M. Cunningham, Yuyan Zheng, Lee Er, Steven Hawken, Yinshan Zhao, Sean J. Barbour
Journal: Journal of the American Society of Nephrology (2022)

Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination.In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available). The primary outcome was disease relapse, on the basis of changes in kidney function, proteinuria, or both. Vaccination was modeled as a 30-day time-varying exposure in extended Cox regression models, stratified on disease type.During 281 days of follow-up, 134 (12.1%) patients experienced a relapse. Although a first vaccine dose was not associated with relapse risk (hazard ratio [HR]=0.67; 95% confidence interval [95% CI], 0.33 to 1.36), exposure to a second or third dose was associated with a two-fold risk of relapse (HR=2.23; 95% CI, 1.06 to 4.71). The pattern of relative risk was similar across glomerular diseases. The absolute increase in 30-day relapse risk associated with a second or third vaccine dose varied from 1%-2% in ANCA-related glomerulonephritis, minimal change disease, membranous nephropathy, or FSGS to 3%-5% in IgA nephropathy or lupus nephritis. Among 24 patients experiencing a vaccine-associated relapse, 4 (17%) had a change in immunosuppression, and none required a biopsy.In a population-level cohort of patients with glomerular disease, a second or third dose of COVID-19 vaccine was associated with higher relative risk but low absolute increased risk of relapse.
Evaluating the Impact of a Biomimetic Mechanical Environment on Cancer Invasion and Matrix Remodeling
Authors: Auxtine Micalet, Judith Pape, Deniz Bakkalci, Yousef Javanmardi, Chloe Hall, Umber Cheema, Emad Moeendarbary
Journal: Advanced Healthcare Materials (2022)

The stiffness of tumors and their host tissues is much higher than most hydrogels, which are conventionally used to study in vitro cancer progression. The tumoroid assay is an engineered 3D in vitro tumor model that allows investigation of cancer cell invasion in an environment that is biomimetic in terms of extracellular matrix (ECM) composition and stiffness. Using this model, the change in matrix stiffness by epithelial colorectal cancer cells is systematically characterized by atomic force microscopy indentation tests. Less invasive epithelial cancer cells stiffen the tumor microenvironment while highly aggressive epithelial cancer cells show significant softening of the tumor microenvironment. Changes in stiffness are attributed to both cell-generated active forces as well as ECM degradation and remodeling. The degradation is in part attributed to the enzymatic activity of matrix metalloproteinases (MMPs) as demonstrated by the significant expression of MMP-2 and MMP-9 at both gene and protein levels. Targeting MMP activity through broad-spectrum drug inhibition (BB-94) reverses the changes in stiffness and also decreases cancer cell invasion. These results promote the idea of using mechano-based cancer therapies such as MMP inhibition.
Lentiviral gene therapy for X-linked chronic granulomatous disease recapitulates endogenous<i>CYBB</i>regulation and expression
Authors: Ryan L. Wong, Sarah Sackey, Devin Brown, Shantha Senadheera, Katelyn Masiuk, Jason P. Quintos, Nicole Colindres, Luke Riggan, Richard A. Morgan, Harry L. Malech, Roger P. Hollis, Donald B. Kohn
Journal: Blood (2022)